CommentaryTime trends and predictors of hypovitaminosis D across the life course: 2009–2016
Introduction
Vitamin D is obtained both from diet and sun exposure, with the most important source being exposure to Ultraviolet B radiation [1,2]. Deficiency in vitamin D has been linked to skeletal abnormalities, rickets and growth problems in children, and to osteomalacia, osteopenia, osteoporosis and skeletal fractures in adults [[3], [4], [5]]. It is also associated with extra-skeletal diseases including autoimmunity, cancer, respiratory diseases and neurologic disorders [6]. Serum 25-hydroxyvitamin D (25OHD) level is currently the best indicator of body vitamin D stores and is thus the marker of interest [2,4,5,7].
There are wide geographic variations in hypovitaminosis D, mostly explained by differences in environmental and, to a lesser extent, genetic factors, in addition to differences in assays used to measure serum 25OHD levels and in the cut-offs selected [4,8,9].
Hypovitaminosis D is common in Eastern and Southern Europe [1,5], Asia [4,8,10] and in the Middle East [1,2,4,5,8,10]. In Europe, specific risk groups include infants and children up to 3 years of age, pregnant women, older persons and non-western immigrants [1]. In a multinational study of 18 countries with various latitudes, conducted on women with osteoporosis, the lowest serum 25OHD levels were recorded in the Middle East [5]. In Lebanon, despite plentiful sunshine, with over 300 sunny days per year, our group reported a high prevalence of 25OHD levels below 20 ng/ml, between the years 2000–2004 (58% in pediatrics, 44% in adults and 41% in elderly) and 2007–2008 (62%, 60% and 62%, respectively) [11]. Predictors of high serum 25OHD level in Lebanon included male sex in children, female sex in adults and elderly, and having measurements taken in summer or fall season [11]. Other known predictors include clothing type, time spent outdoors, pollution and genetic factors [2,5,12].
Interestingly, a clear increase in serum 25OHD levels was noted in the United States after 2007 and coincided with an increase in vitamin D supplementation [13]. Our group observed a similar consistent rise in vitamin D levels in Lebanon between 2000–2004 and 2007–2008, in both sexes, and across all age groups [11].
Great controversy exists with regards to the optimal serum 25OHD level for bone health [8,14,15]. Most guidelines, including the Institute of Medicine (IOM) guidelines reported little or no additional benefit with levels >20 ng/ml [[15], [16], [17]]. However, a level of 30 ng/ml or greater was recommended by the Endocrine Society [18], the International Osteoporosis Foundation [10], the National Osteoporosis Foundation [19] and the American Geriatric Society [20]. Parathyroid hormone (PTH) decline with serum 25OHD increments was used as a surrogate for bone health, to determine the target serum 25OHD levels in different adult and elderly populations [11,21].
The objectives of this follow up study [11] were to assess the prevalence of hypovitaminosis D, define its determinants, and investigate time trends in serum 25OHD levels in Lebanon. We also evaluated the 25OHD-PTH relationship to derive a desirable mean 25OHD in the non-pediatric population.
Section snippets
Study population
We retrieved anonymous demographic and laboratory data of patients, from all age groups, who underwent serum 25OHD measurements at the American University of Beirut -Medical Center (AUB-MC), between January 1st, 2009 and July 19th, 2016, using the digitized database of the Clinical Pathology and Laboratory Medicine department.
In addition to serum 25OHD levels, we collected information on patients' serum calcium (Ca), phosphorus (PO4), alkaline phosphatase (ALKP), PTH, and creatinine (Cr)
Population demographics
The total number of patients who underwent serum 25OHD assessment during our study period was 198,811. After applying the exclusion criteria described in Methods and omitting patients with repeated serum 25OHD measures over consecutive years, we analyzed data from 151,705 patients: 4.6% in 2009, 8.3% in 2010, 13.0% in 2011, 14.3% in 2012, 15.0% in 2013, 16.1% in 2014, 18.1% in 2015, and 10.8% in 2016. Of the total, 6% were children, mean age 11 ± 5 years, 68% were adults, mean age
Discussion
To our knowledge, this is the largest study to investigate hypovitaminosis D and time trends in the Middle East and North Africa (MENA) region, over a large time span, and follows on a similarly conducted study [11]. There was significant increase in mean serum 25OHD levels over an 8 year time span. Our population had a female predominance, and serum 25OHD measurements were mainly performed in an outpatient setting. Overall, the prevalence of low 25OHD levels was 39% at a cutoff of 20 ng/ml,
Authors contribution
Randa K. Saad: Conceptualization, Methodology, Validation, Formal Analysis, Investigating, Data Curation, Writing - Original Draft, Writing - Review & Editing, Visualization. Vanessa C. Akiki: Conceptualization, Methodology, Writing - Original Draft, Writing - Review & Editing. Maya Rahme: Investigation, Data Curation. Mariam Assaad: Investigation, Data Curation. Sara Ajjour: Investigation, Data Curation. Ghada El-Hajj Fuleihan: Conceptualization, Methodology, Validation, Resources, Writing -
Funding
This research received funding from the Medical Practice Plan (MPP) at the American University of Beirut-Medical Center Beirut, Lebanon.
Declaration of competing interest
None. All authors have approved the final article.
Acknowledgments
RS received training under the Scholars in HeAlth Research Program (SHARP), Fogarty International Center and Office of Dietary Supplements of the National Institutes of Health (NIH) under Award Number D43 TW009118. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The authors thank Dr. Laila Al Shaar for her help in finalizing the equation and fitting the curve to define the 25OHD inflection point.
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Randa K. Saad and Vanessa C. Akiki contributed to the manuscript equally.